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Biochem Cell Biol. 2015 Aug;93(4):376-84. doi: 10.1139/bcb-2015-0010. Epub 2015 May 20.

Calcitriol increases Dicer expression and modifies the microRNAs signature in SiHa cervical cancer cells.

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a Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.
e School of Medicine, Universidad Nacional Autónoma de México, Circuito Interior, Ciudad Universitaria, Av. Universidad # 3000, México, D.F. 04510, México.
b Laboratory of Cancer Genomics, Instituto Nacional de Medicina Genómica, Periférico Sur # 4809, Col. Arenal Tepepan, México, D.F. 14610, México.
c Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.
d Evolutionary Genomics Program, Center for Genomic Sciences, Universidad Nacional Autónoma de México, Av. Universidad s/n, Col. Chamilpa, Cuernavaca, Morelos 62210, México.


MicroRNAs play important roles in cancer biology. Calcitriol, the hormonal form of vitamin D3, regulates microRNAs expression in tumor cells. In the present study we asked if calcitriol would modify some of the components of the microRNA processing machinery, namely, Drosha and Dicer, in calcitriol-responsive cervical cancer cells. We found that calcitriol treatment did not affect Drosha mRNA; however, it significantly increased Dicer mRNA and protein expression in VDR-positive SiHa and HeLa cells. In VDR-negative C33-A cells, calcitriol had no effect on Dicer mRNA. We also found a vitamin D response element in Dicer promoter that interacts in vitro to vitamin D and retinoid X receptors. To explore the biological plausibility of these results, we asked if calcitriol alters the microRNA expression profile in SiHa cells. Our results revealed that calcitriol regulates the expression of a subset of microRNAs with potential regulatory functions in cancer pathways, such as miR-22, miR-296-3p, and miR-498, which exert tumor-suppressive effects. In summary, the data indicate that in SiHa cells, calcitriol stimulates the expression of Dicer possibly through the vitamin D response element located in its promoter. This may explain the calcitriol-dependent modulation of microRNAs whose target mRNAs are related to anticancer pathways, further adding to the various anticancer mechanisms of calcitriol.


Dicer; Drosha; VDR; cancer cervical; cervical cancer; microARN; microRNA; vitamin D; vitamine D

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